IWP-3

WNT pathway inhibitor; Inhibits Porcupine

IWP-3

WNT pathway inhibitor; Inhibits Porcupine

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WNT pathway inhibitor; Inhibits Porcupine
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Overview

Inhibitor of WNT Production-3 (IWP-3) inhibits WNT signaling by inactivating Porcupine,  a membrane-bound O-acyltransferase responsible for palmitoylating WNT proteins, which is essential for WNT signaling ability and secretion (Chen et al.).  IWP-3 impairs WNT pathway activity in vitro with an IC₅₀ value of 40 nM (Chen et al.). 

DIFFERENTIATION
· Promotes cardiomyocyte differentiation from human embryonic stem cells that have been induced to mesoderm by addition of BMP4 and Activin A (Willems et al.).
Alternative Names
Inhibitor of Wnt Production-3
Cell Type
Cardiomyocytes, PSC-Derived, Pluripotent Stem Cells
Species
Human, Mouse, Non-Human Primate, Other, Rat
Application
Differentiation
Area of Interest
Stem Cell Biology
CAS Number
687561-60-0
Chemical Formula
C₂₂H₁₇FN₄O₂S₃
Molecular Weight
484.6 g/mol
Purity
≥ 98%
Pathway
WNT
Target
Porcupine

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
IWP-3
Catalog #
72544
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
IWP-3
Catalog #
72544
Lot #
All
Language
English

Applications

This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Resources and Publications

Publications (5)

Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. Willems E et al. Circulation research 2011 AUG

Abstract

RATIONALE: Human embryonic stem cells can form cardiomyocytes when cultured under differentiation conditions. Although the initiating step of mesoderm formation is well characterized, the subsequent steps that promote for cardiac lineages are poorly understood and limit the yield of cardiomyocytes. OBJECTIVE: Our aim was to develop a human embryonic stem cell-based high-content screening assay to discover small molecules that drive cardiogenic differentiation after mesoderm is established to improve our understanding of the biology involved. Screening of libraries of small-molecule pathway modulators was predicted to provide insight into the cellular proteins and signaling pathways that control stem cell cardiogenesis. METHODS AND RESULTS: Approximately 550 known pathway modulators were screened in a high-content screening assay, with hits being called out by the appearance of a red fluorescent protein driven by the promoter of the cardiac-specific MYH6 gene. One potent small molecule was identified that inhibits transduction of the canonical Wnt response within the cell, which demonstrated that Wnt inhibition alone was sufficient to generate cardiomyocytes from human embryonic stem cell-derived mesoderm cells. Transcriptional profiling of inhibitor-treated compared with vehicle-treated samples further indicated that inhibition of Wnt does not induce other mesoderm lineages. Notably, several other Wnt inhibitors were very efficient in inducing cardiogenesis, including a molecule that prevents Wnts from being secreted by the cell, which confirmed that Wnt inhibition was the relevant biological activity. CONCLUSIONS: Pharmacological inhibition of Wnt signaling is sufficient to drive human mesoderm cells to form cardiomyocytes; this could yield novel tools for the benefit of pharmaceutical and clinical applications.
Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Chen B et al. Nature chemical biology 2009 FEB

Abstract

The pervasive influence of secreted Wnt signaling proteins in tissue homeostasis and tumorigenesis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. By screening a diverse synthetic chemical library, we have discovered two new classes of small molecules that disrupt Wnt pathway responses; whereas one class inhibits the activity of Porcupine, a membrane-bound acyltransferase that is essential to the production of Wnt proteins, the other abrogates destruction of Axin proteins, which are suppressors of Wnt/beta-catenin pathway activity. With these small molecules, we establish a chemical genetic approach for studying Wnt pathway responses and stem cell function in adult tissue. We achieve transient, reversible suppression of Wnt/beta-catenin pathway response in vivo, and we establish a mechanism-based approach to target cancerous cell growth. The signal transduction mechanisms shown here to be chemically tractable additionally contribute to Wnt-independent signal transduction pathways and thus could be broadly exploited for chemical genetics and therapeutic goals.
Wnt/beta-catenin signaling in development and disease. Clevers H Cell 2006 NOV

Abstract

A remarkable interdisciplinary effort has unraveled the WNT (Wingless and INT-1) signal transduction cascade over the last two decades. Wnt genes encode small secreted proteins that are found in all animal genomes. Wnt signaling is involved in virtually every aspect of embryonic development and also controls homeostatic self-renewal in a number of adult tissues. Germline mutations in the Wnt pathway cause several hereditary diseases, and somatic mutations are associated with cancer of the intestine and a variety of other tissues.